Lp(a) is a lipoprotein which is highly associated with risk of premature atherosclerotic cardiovascular disease. The protein which identifies this unique lipoprotein is apo(a), which has high homology with plasminogen. Apo(a) is polymorphic, with many different sizes of this protein in the population. This size polymorphism is genetically determined, and in turn, is a major determinant of the plasma level of Lp(a). However, other factors also strongly influence Lp(a) levels but are very poorly understood. The in vivo metabolism of radiolabeled Lp(a) was determined in groups of subjects with the same apo(a) isoform but widely different levels of Lp(a). The catabolic rates of Lp(a) were not significantly different among study subjects, whereas Lp(a) production rates were very different. Therefore, a major factor affecting levels of Lp(a) apart from apo(a) isoform appears to be the rate of production of the Lp(a) lipoprotein. This has important implications for the understanding of Lp(a) metabolism and the clinical approach to patients with high levels of Lp(a) and premature coronary heart disease. These studies included subjects of age 20 to 38 years. 42% of the subjects were women. The studies included one African-American and one Asian subjects.